Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

Role of miR-5010-3p in predicting the prognosis of hepatocellular carcinoma. / MiR-5010-3p在预测肝细胞癌预后中的作用（英文）.

OBJECTIVES: Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma (HCC). However, clinical significance of miR-5010-3p in HCC is not elucidated. This study aims to explore the prognostic value and role of miR-5010-3p in HCC. METHODS: The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis. The Kaplan-Meier, Cox univariate, and Cox multivariate analysis were used to predict its role in the prognosis of HCC. The downstream target genes were predicted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the potential functional pathways they may participate in. Finally, methyl thiazolyl tetrazolium (MTT) assay and 5-ethyl-2'-deoxyuridine (EDU) incorporation experiment were carried out to prove its effect on proliferation. RESULTS: The expression of miR-5010-3p was associated with histological grade (P=0.019), vascular invasion degree (P=0.049), TP53 level (P=0.004), and alpha fetoprotein (AFP) level (P=0.012). A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve (AUC: 0.712, 95% CI 0.649 to 0.776). High expression of miR-5010-3p was associated with shorter overall survival (OS) (P=0.003). The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process. In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells. CONCLUSIONS: MiR-5010-3p promotes the proliferation of liver cancer cells, and its high expression is associated with poor prognosis, which may be a potential prognostic marker.

Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression.

Background: Origin recognition complex 6 (ORC6) is one of the six highly conserved subunit proteins required for DNA replication and is essential for maintaining genome stability during cell division. Recent research shows that ORC6 regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment. Methods: Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of ORC6 in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of ORC6. To evaluate the potential prognostic impact and diagnostic significance of ORC6 expression, we carried out log-rank, univariate Cox regression, and receiver operating characteristic curve analysis. The ICGC-LIRI-JP cohort, CGGA-301 cohort, CGGA-325 cohort, CGGA-693 cohort, and GSE13041 cohort were used for external validation of the study findings. The associations between ORC6 expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to ORC6 expression, gene set enrichment analysis was performed. To clarify the expression and function of ORC6 in hepatocellular carcinoma (LIHC) and glioma, we conducted in vitro experiments. Results: Expression of ORC6 is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, ORC6 may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of ORC6 correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the ORC6 high-expression group benefited from immunotherapy. Inhibiting ORC6 expression suppressed the proliferative and migratory abilities of LIHC and glioma cells. Conclusion: High expression of ORC6 may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of ORC6 may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.

Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma.

Centromere protein F (CENPF), a protein related to the cell cycle, is a key part of the kinetochore-centromere complex involved in cell division, differentiation, and proliferation. CENPF expression is upregulated in various types of cancer and plays a role in oncogenesis and tumor progression. However, the expression pattern, prognostic significance, and biological role of CENPF in these cancer types are poorly understood. Therefore, in this study, we conducted a pan-cancer analysis of the role of CENPF, which we considered a cut point, to investigate its utility as a prognostic and immunological indicator for malignancies, especially cholangiocarcinoma (CCA). Using systematic bioinformatics analysis, we investigated the expression patterns, prognostic relevance, molecular function, signaling pathways, and immune infiltration patterns of CENPF in the pan-cancer analysis. Western blot and immunohistochemistry staining assays were performed to evaluate the expression profiles of CENPF in CCA tissues and cell lines. Furthermore, Cell Counting Kit-8, colony formation, wound healing, and Transwell assays, as well as CCA xenograft mouse models, were employed to determine the role and function of CENPF in CCA. The results showed that CENPF expression was upregulated and strongly linked to a worse prognosis in most cancer types. CENPF expression was substantially associated with immune cell infiltration, tumor microenvironment, genes related to immune checkpoints, tumor mutational burden, microsatellite instability, and immunotherapy response in diverse malignancies. CENPF was considerably overexpressed in CCA tissues and cells. Functionally, inhibiting CENPF expression significantly reduced the proliferating, migrating, and invading abilities of CCA cells. CENPF expression also affects the prognosis of multiple malignancies, which is highly associated with immunotherapy response and tumor immune cell infiltration. In conclusion, CENPF may act as an oncogene and an immune infiltration-related biomarker and can accelerate tumor development in CCA.

Weibo users and Academia's foci on tourism safety: Implications from institutional differences and digital divide.

Tourism safety is essential for tourists and tourism practitioners. This study conducted a bibliometric analysis using VOSviewer and CiteSpace for 2018 articles indexed on the Web of Science (WoS). It also analysed 7293 Weibo posts between 1977 and 2022 using Python, MYSQL, AI sentiment, and Tableau. The first tourism safety publication on WoS appeared in 1977, while the first Weibo microblog dated was dated back to 2011. Compared to the information posted on Weibo, the annual publications about tourism safety on WoS recorded a stable increment. On Web of Science (WoS), the academic staff and universities produced the largest number of tourism safety posts. On the flip side, the most productive organisations on Weibo are government agencies in popular tourism destinations. "Accident", "medical tourism", "environment", "mediating role", and "hospitality" were important burst nodes in tourism safety on WoS. "Quality", "accident", and health-related words were the foci on both Weibo and WoS. On Web of Science, the top 10 most popular keywords of tourism safety-related articles could be classified into two groups: health ("Covid-19", "restoration", "pandemics", "Sars-Cov-2", "Sars", "mental health") and IT terminologies ("big data", "artificial intelligence"). It has been concluded that "artificial intelligence (AI)" is more likely to be included in the keywords on tourism researched by academia. In contrast, the public may not know about or use AI in the tourism industry. Besides, the top 10 most popular keywords on Weibo related to tourism risks and hazards were drowning and traffic risks and hazards, such as drowning and traffic risks. The digital divide may explain such a difference: the academic circle benefits more from the digital age than laypersons. It may also be the result of institutional differences and information asymmetry.

METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer.

BACKGROUND: Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2-) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2- BC initiation and development is still important. METHODS: mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation. RESULTS: Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2- BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2- BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8. CONCLUSION: METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2- BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2- BC.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

Prognostic value of tumor mutation burden and the relationship between tumor mutation burden and immune infiltration in HER2+ breast cancer: a gene expression-based study.

BACKGROUND: Whether tumor mutation burden (TMB) correlated with improved survival outcomes or promotion of immunotherapies remained controversy in various malignancies. We aimed to explore the prognostic value of TMB and the relationship between TMB and immune infiltration in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: We downloaded somatic mutation data and clinical information for 216 HER2+ BC patients from the The Cancer Genome Atlas (TCGA) and cBioPortal databases. Patients were divided into high- and low-TMB groups through TMB calculation. Cox regression analysis was used to establish an immune- and mutant-related risk model based on 5-hub genes. The relationship between 5-hub genes mutants and the level of immune infiltration, as well as the relationship between the risk model and the immune microenvironment were analyzed by "TIMER" database. RESULTS: TMB was negatively correlated with overall survival (OS) and disease-free survival (DFS), and high TMB may inhibit immune infiltration in HER2+ BC. Furthermore, risk score classified effectively patients into low- and high-risk groups in training and validation cohorts. The infiltration of CD4+ T cells and NK cells and the levels of immune checkpoint pathway genes were lower in the high-risk group, which indicated a poor prognosis. CONCLUSIONS: Higher TMB correlated with poor survival outcomes and might inhibit the immune infiltrates in HER2+ BC. The 5-hub TMB-related signature conferred lower immune cells infiltration which deserved further validation.

Construction and validation of a risk prediction model for clinical axillary lymph node metastasis in T1-2 breast cancer.

The current diagnostic technologies for assessing the axillary lymph node metastasis (ALNM) status accurately in breast cancer (BC) remain unsatisfactory. Here, we developed a diagnostic model for evaluating the ALNM status using a combination of mRNAs and the T stage of the primary tumor as a novel biomarker. We collected relevant information on T1-2 BC from public databases. An ALNM prediction model was developed by logistic regression based on the screened signatures and then internally and externally validated. Calibration curves and the area under the curve (AUC) were employed as performance metrics. The prognostic value and tumor immune infiltration of the model were also determined. An optimal diagnostic model was created using a combination of 11 mRNAs and T stage of the primary tumor and showed high discrimination, with AUCs of 0.828 and 0.746 in the training sets. AUCs of 0.671 and 0.783 were achieved in the internal validation cohorts. The mean external AUC value was 0.686 and ranged between 0.644 and 0.742. Moreover, the new model has good specificity in T1 and hormone receptor-negative/human epidermal growth factor receptor 2- negative (HR-/HER2-) BC and good sensitivity in T2 BC. In addition, the risk of ALNM and 11 mRNAs were correlated with the infiltration of M2 macrophages, as well as the prognosis of BC. This novel prediction model is a useful tool to identify the risk of ALNM in T1-2 BC patients, particularly given that it can be used to adjust surgical options in the future.

Prognosis Comparison Between Nipple-Sparing Mastectomy and Total Mastectomy in Breast Cancer: A Case-Control Study After Propensity Score Matching.

BACKGROUND: Currently, the operation rate of nipple-sparing mastectomy (NSM) is increasing. However, the long-term prognosis of NSM is not well documented. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term prognosis of NSM compared with total mastectomy (TM). METHODS: Population-level data of female breast cancer patients treated with NSM and TM were extracted from 1998 to 2016 from the SEER database. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables in comparisons. Kaplan-Meier analysis, log-rank test, and Cox proportional hazard regression were performed. RESULTS: A total of 5765 patients underwent NSM, which increased from 266 in 2004-2009 to 5370 in 2010-2016. A total of 134,528 patients underwent TM, and the number of patients undergoing TM continued to decline. The overall survival (OS) and breast cancer-specific survival (BCSS) were similar between the NSM group and the TM group (P = 0.058 and 0.87, respectively). For OS, subgroup analysis showed that patients with age ≥ 46, White race, median household income ≥ $70,000, hormone receptor-positive, and HER2 negative had a better prognosis for treatment with NSM. There was no significant difference in BCSS between the NSM group and the TM group. CONCLUSIONS: In recent years, the clinical application of NSM has been increasing. NSM is a proper procedure for breast cancer patients to achieve long-term survival.

Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers.

BACKGROUND: The cumulative risk of distant recurrence of hormone receptor-positive (HR+) breast cancer in the past 20 years has ranged from 22% to 52% after 5 years of endo-therapy. The TNM stage, histological grade, and age are important clinical factors related to recurrence, however the exact mechanism of tamoxifen resistance is still unclear. METHODS: Differentially expressed genes (DEGs) were identified in 10 pairs of patients who had relapsed and non-relapsed after tamoxifen treatment based on matching their clinicopathological factors. After analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 10 hub genes were identified using Cytoscape software. Next, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used to verify the expression and overall survival (OS) of the 10 hub genes respectively, and GSE96058 and Kaplan-Meier Plotter website were used to further verify the OS of C3, CX3CL1, CXCL2, and SAA1. Finally, Immune Cell Abundance Identifier (ImmuCellAI) and the TIMER database were used to estimate immune cell infiltration and the expression of prognostic genes. RESULTS: The DEGs were mainly enriched in the inflammatory response and cytokine-receptor interaction. The expression and the survival analysis identified CX3CL1, CXCL2, and SAA1 as prognostic factors, whose overexpression in HR+/human epidermal growth factor receptor 2 (HER-2) negative breast cancer possibly predicted a longer disease-free survival. The expression levels of these 3 genes are positively correlated with immune cell infiltration. Their high expression levels may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be biomarkers for tamoxifen-resistant therapy. CONCLUSIONS: In conclusion, the high expression of CX3CL1, CXCL2, and SAA1 may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

Inhibition of autophagy with Chloroquine enhanced apoptosis induced by 5-aminolevulinic acid-photodynamic therapy in secondary hyperparathyroidism primary cells and organoids.

Secondary hyperparathyroidism (SHPT), the most common complication in the later stage of chronic kidney disease (CKD), seriously affects quality of life and the survival time of patients. At present, the conventional drugs and surgical methods still cannot fully meet the needs of clinical treatment. It is quite significant to develop effective and minimally invasive treatment methods. 5-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT), an alternative treatment relying on light irradiation, photosensitizer, and oxygen to produce a series of cytotoxic effects on tissue, is a promising technique for treating SHPT. We have successfully cultivated SHPT primary cells and organoids, and further proved that the amount of 5-ALA transformed into protoporphyrin IX in a time- and concentration-dependent manner. Also, 5-ALA-PDT exerted a cytotoxic effect on both primary cells and organoids by the cell counting kit (CCK-8) assay. Mechanically, 5-ALA-PDT increased the number of autophagosomes, and autophagy- and apoptosis-related proteins were upregulated markedly by western-blotting. The autophagy inhibitor Chloroquine (CQ) significantly increased the proportion of apoptotic cells, while the autophagy inducer rapamycin decreased the inhibitory ability of 5-ALA-PDT in SHPT primary cells. In brief, 5-ALA-PDT exhibits a phototoxic effect on SHPT primary cells and organoids. Autophagy and apoptosis are involved in the mechanism, and autophagy plays a role in promoting survival and inhibiting apoptosis. Therefore, the use of autophagy inhibitors can increase the sensitivity of SHPT cells and organoids treated with 5-ALA-PDT.

Long non­coding RNA SNHG1 promotes breast cancer progression by regulation of LMO4.

Long non­coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) was reported to be a critical regulator of tumorigenesis and is frequently deregulated in several cancer types. However, the exact mechanism by which SNHG1 contributes to breast cancer progression has not been fully elucidated. The identification of the molecular mechanism of SNHG1 is important for understanding the development of breast cancer and for improving the prognosis of the patients with this disease. In the present study, increased expression levels of SNHG1 were noted in breast cancer tumors following analysis of differentially expressed lncRNAs between 1,063 tumor and 102 normal tissues derived from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA­BRCA) dataset. This finding was further validated using 50 pairs of normal and tumor tissues that were collected from patients with breast cancer. Notably, SNHG1 expression was significantly correlated with estrogen receptor (ER)/progesterone receptor (PR) negative status (ER­/PR­) and advanced clinical stage in breast cancer tissues. Knockdown of SNHG1 led to cell growth arrest, cell cycle redistribution and cell migration inhibition of breast cancer cells. The miRDB database predicted that miR­573 interacts with SNHG1. RT­PCR confirmed the negative regulation of miR­573 levels by SNHG1 in breast cancer cells and the Dual­luciferase reporter assay confirmed their complementary binding. The repression of miR­573 by SNGH1 decreased LIM domain only 4 (LMO4) mRNA and protein expression levels in the breast cancer cell lines tested and induced the expression of cyclin D1 and cyclin E. In vitro experiments indicated that LMO4 overexpression could reverse siSNHG1­induced cell growth arrest, cell cycle redistribution and inhibition of cell migration in breast cancer cells. Moreover, the tumor xenograft model indicated that SNHG1 knockdown inhibited MDA­MB­231 growth in vivo and LMO4 overexpression reversed the tumor growth inhibition induced by SNHG1 knockdown. The present study demonstrated that SNHG1 acts as a novel oncogene in breast cancer via the SNHG/miR­573/LMO4 axis and that it could be a promising therapeutic target for patients with breast cancer.

Impact of death education courses on emergency nurses' perception of effective behavioral responses in dealing with sudden death in China: A quasi-experimental study.

BACKGROUND: Nurses in emergency departments have to provide rescue care and life support for moribund patients, but also emotional support to patients' relatives. On the other hand, emergency nurses are also the most vulnerable to the sudden death of patients. Nurses working in the emergency department were invited to participate in a death education course. OBJECTIVE: To explore the impact of a death education course on the emergency nurses' perception of effective behavioral responses in dealing with sudden death. DESIGN: A quasi-experimental study. SETTINGS: A level A tertiary general hospital in China. PARTICIPANTS: A total number of 34 emergency nurses who met the inclusion criteria were randomly selected from the emergency department. METHODS: Participants received a death education course of 20 credit hours based on dealing with a sudden-death model. The general data questionnaire and the Chinese version of the list proposed by Fraser & Atkins were completed before the intervention and six weeks post-intervention. The scores of each item in the effective behavioral response to the sudden death questionnaire of the emergency nurses before and after the intervention were compared. RESULTS: After the intervention, the nurses considered that 10 items were relatively helpful (above 4 points) and 2 items relatively less helpful (<3 points). The post-intervention average scores of all items were higher than the pre-intervention ones, and there were significant differences in the scores of the 13 items pre- and post-intervention. CONCLUSION: The death education course enhanced emergency nurses' perceptions of effective behavioral responses in dealing with sudden death, which contributes to the improvement of the quality of their work.

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis.

BACKGROUND: Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. METHODS: This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. RESULTS: A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. CONCLUSION: For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

[Effect of Step Feed on Denitrifying Phosphorus and Nitrate Removal in a Modification of the Two Sludge A2/O-BAF System].

A modification of the two sludge A2/O-BAF system was used to treat low C/N real domestic sewage. In order to improve the utilization of the carbon source, the effects of two step feeds (pre-anoxic zone and anoxic zone) on denitrifying phosphorus and nitrate removal were studied. According to the formula of material balance for COD, the utilization of carbon source was analyzed and evaluated under different ratios of step feed, simultaneously. The results showed that when the ratio of step feed was 7:3 and the influent concentrations of COD, NH4+-N, TN, and TP were 174.99, 58.19, 59.10, and 5.15 mg·L-1, respectively, their effluent concentrations were 29.48, 4.07, 14.10, and 0.40 mg·L-1, and the removal rates were 82.12%, 92.76%, 75.45%, and 91.20%, respectively. It was found that when the ratio of the denitrifying phosphorus accumulation organisms to the phosphorus accumulation organisms(DPAOs/PAOs) was 98.81%, the efficiencies of denitrifying phosphorus and nitrate removal were optimum. By optimizing step feed, the carbon source was utilized effectively, and the efficiencies of nitrogen and phosphorus removal were improved simultaneously. The theoretical basis has thus been provided for the modification of the two sludge A2/O-BAF system to treat low C/N waste water.

Dynamics of Gut Microbiome in Giant Panda Cubs Reveal Transitional Microbes and Pathways in Early Life.

Adult giant pandas (Ailuropoda melanoleuca) express transitional characteristics in that they consume bamboos, despite their carnivore-like digestive tracts. Their genome contains no cellulolytic enzymes; therefore, understanding the development of the giant panda gut microbiome, especially in early life, is important for decoding the rules underlying gut microbial formation, inheritance and dietary transitions. With deep metagenomic sequencing, we investigated the gut microbiomes of two newborn giant panda brothers and their parents living in Macao, China, from 2016 to 2017. Both giant panda cubs exhibited progressive increases in gut microbial richness during growth, particularly from the 6th month after birth. Enterobacteriaceae dominated the gut microbial compositions in both adult giant pandas and cubs. A total of 583 co-abundance genes (CAGs) and about 79 metagenomic species (MGS) from bacteria or viruses displayed significant changes with age. Seven genera (Shewanella, Oblitimonas, Helicobacter, Haemophilus, Aeromonas, Listeria, and Fusobacterium) showed great importance with respect to gut microbial structural determination in the nursing stage of giant panda cubs. Furthermore, 10 orthologous gene functions and 44 pathways showed significant changes with age. Of the significant pathways, 16 from Escherichia, Klebsiella, Propionibacterium, Lactobacillus, and Lactococcus displayed marked differences between parents and their cubs at birth, while 29 pathways from Escherichia, Campylobacter and Lactobacillus exhibited significant increase in cubs from 6 to 9 months of age. In addition, oxidoreductases, transferases, and hydrolases dominated the significantly changed gut microbial enzymes during the growth of giant panda cubs, while few of them were involved in cellulose degradation. The findings indicated diet-stimulated gut microbiome transitions and the important role of Enterobacteriaceae in the guts of giant panda in early life.

Genomic and transcriptome analysis revealing an oncogenic functional module in meningiomas.

OBJECT: Meningiomas are among the most common primary adult brain tumors. Although typically benign, roughly 2%-5% display malignant pathological features. The key molecular pathways involved in malignant transformation remain to be determined. METHODS: Illumina expression microarrays were used to assess gene expression levels, and Illumina single-nucleotide polymorphism arrays were used to identify copy number variants in benign, atypical, and malignant meningiomas (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression data sets generated on Affymetrix microarrays (n = 68, including 6 malignant ones; n = 56, including 3 malignant ones). A weighted gene coexpression network approach was used to identify coexpression modules associated with malignancy. RESULTS: At the genomic level, malignant meningiomas had more chromosomal losses than atypical and benign meningiomas, with average length of 528, 203, and 34 megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one of the primary chromosomal level abnormalities in all subtypes of meningiomas. At the transcriptome level, the authors identified 23 coexpression modules from the weighted gene coexpression network. Gene functional enrichment analysis highlighted a module with 356 genes that was highly related to tumorigenesis. Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were oncogenic in other cancers such as leukemia. A putative meningioma tumor suppressor MN1 was also identified in this module with differential expression between malignant and benign meningiomas. CONCLUSIONS: The authors' genomic and transcriptome analysis of meningiomas provides novel insights into the molecular pathways involved in malignant transformation of meningiomas, with implications for molecular heterogeneity of the disease.

[Self-management behaviors in patients with osteoarthritis].

Good self-management behaviors can control symptoms of the patients with osteoarthritis, improve the patients' joint function and quality of life. Patients' self-management behaviors have been impacted by disease knowledge, self-efficacy, emotional state, and social support. All the above factors should been taken into full consideration when intervening. Self-management program is an intervention mode which can improve patient self-management behaviors and promote patient health.

Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.

Exonic deletions in NRXN1 have been associated with several neurodevelopmental disorders, including autism, schizophrenia and developmental delay. However, the molecular mechanism by which NRXN1 deletions impact neurodevelopment remains unclear. Here we used human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) as models to investigate the functional impacts of NRXN1 knockdown. We first generated hiPSCs from skin fibroblasts and differentiated them into neural stem cells (NSCs). We reduced NRXN1 expression in NSCs via a controlled shRNAmir-based knockdown system during differentiation, and monitored the transcriptome alteration by RNA-Seq and quantitative PCR at several time points. Interestingly, half reduction of NRXN1 expression resulted in changes of expression levels for the cell adhesion pathway (20 genes, P = 2.8×10(-6)) and neuron differentiation pathway (13 genes, P = 2.1×10(-4)), implicating that single-gene perturbation can impact biological networks important for neurodevelopment. Furthermore, astrocyte marker GFAP was significantly reduced in a time dependent manner that correlated with NRXN1 reduction. This observation was reproduced in both hiPSCs and hESCs. In summary, based on in vitro models, NRXN1 deletions impact several biological processes during neurodevelopment, including synaptic adhesion and neuron differentiation. Our study highlights the utility of stem cell models in understanding the functional roles of copy number variations (CNVs) in conferring susceptibility to neurodevelopmental diseases.